Neuromuscular blocking drugs, or muscle relaxants, are widely used by anesthetists for producing muscle relaxation during anesthesia and surgery. Controlled muscle paralysis in the patient is commonly used for tracheal intubation, surgical relaxation and to permit controlled breathing in thoracic surgical procedures.
Muscle relaxants may be classified as either competitive non-depolarizing) or non-competitive (depolarizing) agents. Non-depolarizing relaxants compete with acetylcholine for receptor sites located at the myoneural junction, and block muscle contraction in response to acetylcholine released following nerve stimulation. Depolarizing relaxants, conversely, have an action similar to that of acetylcholine, and block by persistent depolarization of muscle tissue. With both type of relaxants, neuromuscular block persists as long as the quantity of relaxant introduced into the patient has not been completely bound or metabolized.
The type (depolarizing or non-depolarizing) and the magnitude of neuromuscular block can be assessed by stimulating a peripheral motor nerve and observing or measuring the force of contraction of the muscle supplied by that nerve. This is usually done in a clinical setting by stimulating the ulnar nerve at the wrist or elbow and monitoring the force of contraction (adduction) of the thumb as the adductor pollicis muscle contracts. The force of contraction is measured using a force-displacement transducer which provides an electrical output signal proportional to the force supplied by the thumb during contraction.
The pattern of evoked muscle response to changes in the frequency of the electrical stimulation allows the type and quantitative level of neuromuscular block to be determined. Stimuli commonly used include (1) short durartion, single pulses, which yield a twitch response, (2) a train of four pulses at short intervals which produce a train of four responses, and (3) a five second period of application of a rapid succession of pulses (e.g., at pulse frequencies 30, 50, 100 or 200 Hz) which produces a tetanic response.
When single twitch responses are to be observed in a clinical setting, a control response is obtained by applying a supramaximal, square-wave stimulus (preferably no longer than 200 microseconds in duration) prior to the administration of the muscle relaxant and measuring the magnitude of the resulting response. The responses that are obtained to the pulse stimuli following the administration of relaxants are compared to the control response, and the degree of depression of muscle response is estimated or quantitated by comparing the magnitude of the responses obtained to the magnitude of the control response. A major disadvantage of using a single twitch response to estimate the level of neuromuscular block is that a control response must be obtained before a muscle-relaxant, or any other anesthetic drug, is administered.
The need for first obtaining a control response may be eliminated if a train-of-four stimulation procedure is used. Four pulses are applied in succession at 2 Hz, and the amplitude of the fourth twitch response during supramaximal stimulation is compared to the amplitude of the first twitch response; the ratio between the two (T.sub.4 ratio) is then calculated to provide an estimate of the level of twitch height depression. The estimate of the level of single twitch height depression can then be correllated with clinical neuromuscular functions such as adequacy of respiration, cough response, and surgical relaxation. A T.sub.4 ratio greater than 75% indicates normal neuromuscular function, while a ratio less than 75% indicates the presence of impaired function. The estimate of twitch height depression when the T.sub.4 ratio is less than 75% may be further quantitated by noting the presence or absence of twitch responses following the first, second, and third pulse stimuli in a train-of-four pulses.
Tetanic stimulation is the most sensitive clinically employed test of neuromuscular function. The tetanic response may be obtained by applying 5 seconds of supermaximal pulse stimulation at frequencies of 30, 50, 100, or 200 Hz. The ability of the muscle to sustain contraction during tetanic stimulation varies with the level of neuromuscular block. In addition to the need for an awake control response, major disadvantages of tetanic stimulation are that it alters neuromuscular function and is painful to patients who are awake. These disadvantages make it difficult to quantitate the degree of neuromuscular block with tetanic stimulation and tetanic stimulation is presently used mainly for clinical research.
In current clinical practice, the degree of neuromuscular block is most commonly estimated by observing and qualitatively assessing the muscle response following single twitch or train-of-four stimulation. While this method is imprecise and not totally satisfactory, currently available apparatus for quantitatively assessing neuromuscular function are relatively costly and difficult for the clinician to use.